Elsevier

Oral Oncology

Volume 35, Issue 3, May 1999, Pages 273-277
Oral Oncology

Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy

https://doi.org/10.1016/S1368-8375(98)00115-8Get rights and content

Abstract

Of all the clinical disciplines, radiotherapy probably has the most secure and scientific foundations. In oral cancer, radiotherapy may be used as the sole treatment or in combination with other modalities of treatment. Blood samples were collected from stage III oral cancer patients attending the Oncology Department, Bernard Institute of Radiation and Oncology, Chennai Medical College, Chennai, India, before initiating radiotherapy and after the sixth week of radiotherapy. The effect of radiation on oral cancer patients has been studied using activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) and levels of malondialdehyde (MDA). The levels of MDA showed a significant increase in untreated and radiation oral cancer patients when compared with normal subjects. The activities of red blood cell (RBC) hemolysate antioxidant enzymes such as SOD, catalase, GPX, GR, GST and G6PDH showed a significant decrease, representing the lack of antioxidant defense. Radiation induces lipid peroxidation by inactivating the antioxidant enzymes, thereby rendering the system inefficient in management of the free radical attack. Thus, the degree of radiation affects the extent of the depression of the antioxidant enzyme activities and increases lipid peroxidation.

Introduction

Oral cancer appears to be one of the major causes of misery and death. Though radiotherapy is one of the clinical means by which oral cancer can be treated, many biochemical complications, such as damage to cellular DNA[1]and membrane structures, and alterations in the immune system[2], arise as a result of radiation treatment. The biological effects they produce are thought mainly to be caused by the production of free radicals from interaction with the cell constituents, especially water[3]. Oxygen, normally present in most biological systems, aggravates the damage done by radiation. Much of the initial damage done is due to the formation of hydroxyl radicals, which can react with other cellular components to produce organic radicals[4]. One of the important underlying phenomena is an oxidative change in the membrane lipids, which may be triggered by free radicals.

Radiation chemistry represents a convenient method to selectively generate and study individual reactive free radical species in order to evaluate their potential involvement in biochemical cytotoxicity[5]. Gamma irradiation of erythrocytes induces alterations at three different functional units of the membrane: (1) the lipid bilayer, (2) the protein components and glycocalyx, and (3) the cytoskeleton at the membrane surfaces[6]. Lipid peroxidation is initiated by very potent free radicals, which include superoxide (O2) and hydroxyl radicals (OH) and the reactive molecule hydrogen peroxide (H2O2). Hydrogen peroxide and O2 may be directly damaging or more often interact to form a highly reactive species that can attack almost every molecule in living cells[7]. The well-characterised product of lipid peroxidation is malondialdehyde (MDA), which has been shown to react with nucleic acids, possibly contributing to mutagenesis and carcinogenesis[8]. The peroxidation of unsaturated lipids in natural membrane results, at moderate doses, in an increased rigidity of the hydrophobic region of the lipid bilayer and an increased permeability to different solutes whilst, at high doses, a destruction of the membrane structure with consequent erythrocyte hemolysis is observed9, 10. The oxidation of erythrocytes by H2O2 has been known to induce hemolysis and membrane damage. The normal formation of O2 from hemoglobin exposes the cell to a constant mild oxidative stress. In addition, the lack of biosynthetic capacity of the erythrocyte means that membrane lipids or proteins damaged by lipid peroxidation are not easily replaced[11].

Numerous enzymatic and non-enzymatic mechanisms protect the cell against oxidative injury. The removal of damaging oxygen products is catalysed by antioxidant enzymes and they play a major role in protecting the cell from the oxidative damage caused by free radicals. Non-enzymatic defences are provided by antioxidant molecules—vitamins A, C, E, glutathione, ceruloplasmin and selenium. Antioxidants have been shown to inhibit both initiation and promotion in carcinogenesis and counteract cell immortalisation and transformation[12]. Since the deleterious effects produced by the free radicals depend upon the balance between the oxidant and antioxidant capacity of the system, it was decided to study the relationship between free radicals, antioxidant enzymes, malignancy and cytotoxic effect of radiation. A comparative picture of oxidant and antioxidants in normal, untreated and radiation-treated oral cancer patients is presented here.

Section snippets

Materials and methods

Blood samples were obtained from stage III oral cancer patients who were admitted to the Oncology Department, Bernard Institute of Radiation and Oncology, Chennai Medical College, Chennai, India, after overnight fasting. The patients were taken for investigation on confirmation by histopathological examination of the biopsy sample. Blood was collected before initiating radiotherapy and after the sixth week of radiotherapy. Radiotherapy was given with a Telecobalt beam using anterior and lateral

Results

Fig. 1 shows MDA levels in the serum, erythrocyte and erythrocyte membrane of Group I, Group II and Group III patients. Circulating levels of MDA showed significant increases in Group II (p<0.01) and Group III (p<0.001) when compared with normal subjects. Among oral cancer patients, Group III patients had higher MDA levels than Group II patients.

The activities of RBC hemolysate antioxidant enzymes such as SOD, catalase and G6PDH showed a significant decrease in Group II (p<0.01) and Group III

Discussion

Increased lipid peroxidation in abnormally proliferating cells leads to an increase in serum lipid peroxides in cancer patients. The increase in lipid peroxidation in cancer may also be due to the poor antioxidant system as observed by Szatrowski and Nathan[21]. Radiation induces free radicals which in turn induce MDA levels[22]. Increase in MDA in oral cancer patients might be due to the decomposition products of polyunsaturated fatty acids (PUFAs) of biomembranes. Similar observations have

Acknowledgements

K.E. Sabitha acknowledges financial assistance from the Council of Scientific and Industrial Research, New Delhi, India.

References (38)

  • A. Bonincontro et al.

    Alteration of membrane conductivity and fluidity in human erythrocyte membranes and erythrocyte ghosts following gamma-irradiation

    International Journal of Radiation Biology

    (1987)
  • Halliwell B, Gutteridge JMC. In: Production of Hydroxyl Radicals in Living Systems. Free Radicals in Biology and...
  • Bases AK, Maruett IJ. Cancer Research...
  • T. Nakazawa et al.

    Radiation induced lipid peroxidation and membrane permeability in liposomes

    International Journal of Radiation Biology

    (1980)
  • Halliwell B, Gutteridge JMC. Production of Hydroxyl Radicals in Living Systems. Free Radicals in Biology and Medicine....
  • Freisen M., Manu G., Busachini V., Bartsch H., Nair U., Nair J., Floyd R.A.. IARC Science Publications...
  • T.S. Vematsu et al.

    Serum lipid peroxide level in patients suffering from liver disease

    Clinica Chemica Acta

    (1977)
  • H.P. Mizra et al.

    The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase

    Journal of Biological Chemistry

    (1972)
  • A.K. Shina

    Calorimetric assay of catalase

    Analytical Biochemistry

    (1972)
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